Small animal imaging systems are rapidly becoming integral elements of many biomedical research programs, allowing the detailed study of animal models of a number of diseases. Recently, the multimodality imaging techniques originally developed for clinical use have been applied to pre-clinical applications. In this project we propose to create a combined MRI-PET imaging insert designed for quantitative contemporaneous imaging of small animals using a 3T clinical MRI. Thus, MRI-PET imaging can be made available to researchers who do not have access to the current generation of MRI-PET inserts designed for specialized high field, small animal MRI systems optimized for the imaging of mice. The MR-compatible PET component of the system will utilize continuous blocks of scintillator, coupled to microchannel plate, position-sensitive photomultiplier tubes (MCP- PSPMTs) located outside the bore of the MRI system via short fiber optic light guides. The use of light guides allows us to use high gain, large area photomultiplier tubes, which will maximize the field-of-view (FOV) of the PET to facilitate rapid imaging of animal species larger than mice (rats to rabbits). This capability is likely to be very important in the near future since a number of important disease models in these species have been developed and may be preferable to some mouse models. In addition, since there are no sensitive electrical components in the imaging area of the MRI scanner, no electrical shielding is required. Thus, there will be no conductive material in the MRI FOV that may produce eddy currents, which have been shown to affect MRI SNR. Degradation in some PET imaging performance metrics caused by attenuation of signal in the light guides will be offset by the use continuous blocks of a very high light output scintillator (LaBr3). Application of continuous block scintillator permits us to measure depth of photon interaction by using the shape of the light pulses. Furthermore, our system will include a rotating photon source in its design that will facilitate correction of photon attenuation effects. This capability is critical if the PET images are to be used for quantification of radiotracer concentration. In parallel, two custom transmit/receive MRI coil sets will be developed and tested. One coil set is designed for optimal MR imaging of rats, while the other is intended for animals up to the size of rabbits. MRI methods for acquiring anatomical, functional and spectroscopic MR data will be adapted for use with our new system. In addition, techniques will be implemented for segmenting the MRI images and co- registering the MRI, fMRI, and PET images. Finally, in addition to initial phantom testing, a small number of rats and rabbits will be imaged to demonstrate the imaging capabilities of the new system. The novel aspects of this device include the use continuous blocks of LaBr3, application of MCP-PSPMTs to create a large FOV MRI-PET system, acquisition of transmission scans for attenuation correction, implementation of PET image reconstruction methods that utilize structural information from MRI images and the development of interchangeable MRI-RF coils to fit the size of the animal species under investigation. At the completion of this project we will have built and initially tested a large FOV MRI-PET insert for use in clinical MRI 3T scanners, making this state-of-the-art technology available to an expanded number of researchers utilizing pre-clinical imaging techniques. PUBLIC HEALTH RELEVANCE: This application proposes the development of a large field-of-view combined MRI-PET animal imaging system. This device could be instrumental in the discovery of new drugs and methods to aid in the diagnosis and treatment of a large number of diseases.